Cyclopropanecarboxylate pesticides and their preparation

ABSTRACT

Compounds of the formula ##STR1## wherein R 1  is an acyl group or certain optionally halo-substituted hydrocarbyl groups, and X is --CH 2  CH(OCH 3 ) 2 , --CH 2  CHO, --CH═CHOR 2  in which R 2  is acyl, --CHO,--C(O)Cl, --C(O)Br or --C(O)OR in which R is H, a salt-forming cation, an alkyl group or the residue of a pyrethroid alcohol are new pesticides or intermediates therefore. The compounds are prepared using a multi-step synthesis starting from the natural terpene, 3-carene.

This is a division of application Ser. No. 953,987 filed Oct. 23, 1978abandoned.

FIELD OF THE INVENTION

The present invention is directed to new cyclopropanecarboxylatepesticides, their use in pest control, to pest control formulationscontaining the new cyclopropanecarboxylates, to processes forpreparation of these cyclopropanecarboxylates and to novelintermediates.

SUMMARY OF THE INVENTION

The present invention relates to new cyclopropane compounds of theformula ##STR2## wherein R¹ represents an acyl group containing from 1to 10 carbon atoms; an alkyl group containing from 1 to 10 carbon atomsoptionally substituted by one or more halogen atoms; a (cycloalkyl)alkylgroup containing from 3 to 7 ring carbon atoms, a total of from 4 to 9carbon atoms and optionally ring-substituted by one or more halogenatoms; a cycloalkyl group containing from 3 to 7 ring carbon atoms; analkenyl group containing from 2 to 4 carbon atoms optionally substitutedby one or more halogen atoms; an alkynyl group containing from 2 to 4carbon atoms or an aryl group containing from 6 to 12 carbon atoms or anaralkyl group containing from 7 to 10 carbon atoms, each optionallyring-substituted by one or more halogen atoms;

X is --CH₂ CH(OCH₃)₂, --CH₂ CHO, --CH═CHOR² in which R² is an acyl groupcontaining from 1 to 5 carbon atoms, --CHO, --C(O)Cl, --C(O)Br, or--C(O)OR in which R represents a hydrogen atom, a salt-forming cation,an alkyl group containing from 1 to 20 carbon atoms or a group of theformula ##STR3## wherein Y represents hydrogen or an alkyl, alkenyl oralkynyl group or an aryl or furyl group which is unsubstituted orsubstituted in the ring by one or more alkyl, alkenyl, alkoxy orhalogeno groups, R⁷ and R⁸, which may be the same or different, eachrepresents hydrogen or an alkyl or alkenyl group. R⁹ represents hydrogenor a methyl group, R¹⁰ and R¹¹ represent hydrogen or an alkyl group, R¹²represents an organic radical having carbon-carbon unsaturation in aposition α to the CH₂ group to which R¹² is attached, A/S indicates anaromatic ring or a dihydro or tetrahydro analog thereof, X¹, X², X³ andX⁴, which may be the same or different, each represent hydrogen, halogenor a methyl group, D represents H, ##STR4## in which R¹³ and R¹⁴ may bethe same or different, each represent a hydrogen atom or an alkyl groupcontaining from 1 to 10 carbon atoms, Z represents --CH₂ --, --O--,--CO--, or --S--, Z¹ and Z², which may be the same or different, eachrepresent halogen or an alkyl group containing 1 to 4 carbon atoms and nis 0, 1 or 2, with the proviso that when D is ##STR5## then the alcoholmoiety is in the R,S-racemic or in the S-optical configuration.

The above esters of the present invention wherein X is C(O)OR in which Ris a group of formula I, II, III, IV, V or VI are useful pest controlagents.

The other cyclopropane compounds described above are usefulintermediates for the production of the pest control esters.

A preferred subclass of compounds of the invention are those wherein R¹is an alkyl group containing from 1 to 6 carbon atoms; a(cycloalkyl)alkyl group containing from 3 to 6 ring carbon atoms and 4to 8 carbon atoms in the group; a cycloalkyl group containing from 3 to6 carbon atoms; an alkenyl or alkynyl group containing from 2 to 4carbon atoms; an aryl group containing from 6 to 12 carbon atoms or anaralkyl group containing from 7 to 10 carbon atoms and X is --C(O)OR inwhich R is phenoxybenzyl or especially α-cyano-3-phenoxybenzyl. Thecompounds wherein R¹ is an alkyl of from 1 to 3 carbon atoms, especiallyethyl, have been found to have insecticidal activity, e.g., against cornearworm larvae.

The cyclopropane compounds exhibit optical isomerism by virtue of twoasymmetric centers in the cyclopropane ring and consequently can beprepared in optically active forms, which can subsequently be mixedtogether, or as racemic mixtures, which can subsequently be resolvedinto optically active forms. Because they usually provide the highestdegree of pest control, the (1R,cis) esters are preferred although the(1R,trans) esters are also active. In the esters of α-substitutedalcohols in which D in formulas I or IV is other than hydrogen, there isa further possibility of optical isomerism, i.e., as R or as S opticalconfiguration. The esters in which these alcohols exist in the R opticalconfiguration are without practical pest control activity.

The invention also relates to processes for preparing the new pestcontrol cyclopropanecarboxylates described above from 3-carene. When(+)-Δ³ -carene is used the pesticidal ester products have the (1R,cis)optional configuration.

Basically, the hydrocarbyloxymethyl-2,2-dimethylcyclopropanecarboxylicacids are prepared by a multi-step process in which 3-carene having theformula VII ##STR6## is ozonized and treated with dimethyl sulfide inmethanol to form1-(2,2-dimethoxyethyl)-2,2-dimethyl-3-(2-oxopropyl)cyclopropane, a novelchemical having the formula VIII, ##STR7## which is oxidized to(2-(2,2-dimethoxyethyl)-3,3-dimethylcyclopropyl)methyl acetate havingthe formula IX ##STR8## Hydrolysis of the above acetate derivativeyields (2,2-dimethyl-3-(2,2-dimethyloxyethyl)cyclopropyl)methanol havingthe formula X. ##STR9## The above compound is converted to a compoundhaving the formula XI ##STR10## wherein R¹ is an optionally substitutedhydrocarbyl group as described earlier. Hydrolysis of the above compoundyields an aldehyde derivative having the formula XII, ##STR11## whichreacts with a carboxylic acid anhydride, e.g., acetic anhydride, toproduce a 2-(2,2-dimethyl-3-(hydrocarbyloxymethyl)cyclopropyl)vinylester having the formula XIII ##STR12## wherein R² is an acyl groupcontaining from 1 to 5 carbon atoms. Ozonolysis of the above vinyl esterderivative and treatment with zinc forms a2,2-dimethyl-3-(hydrocarbyloxymethyl)cyclopropanecarboxaldehyde havingthe formula XIV. ##STR13## Oxidation of the above compound of formulaXIV yields a 2,2-dimethyl-3-(hydrocarbyloxymethyl)cyclopropanecarboxylicacid, useful for the preparation of ester pest control agents of theinvention wherein R¹ is an optionally substituted hydrocarbyl group asdescribed above and X is --C(O)OR in which R is a group of formulasI-VI, inclusive.

The acetoxymethyl-2,2-dimethylcyclopropanecarboxylic acid is prepared bya multi-step process in which 3-carene is ozonized and treated withdimethyl sulfide in methanol to form1-(2,2-dimethoxyethyl)-2,2-dimethyl-3-(2-oxopropyl)cyclopropane asdescribed earlier. This product is oxidized to(2-(2,2-dimethoxyethyl)-3,3-dimethylcyclopropyl)methyl acetate IX asdescribed earlier. This acetate derivative is hydrolyzed in the presenceof acid to (2,2-dimethyl-3-(2-oxoethyl)cyclopropyl)methyl acetate havingthe formula XV ##STR14## Treatment of the above compound with aceticanhydride in the presence of a base produces2-(3-acetoxymethyl-2,2-dimethylcyclopropyl)vinyl acetate having theformula XVI ##STR15## Ozonolysis and treatment with zinc of the abovevinyl acetate derivative yields3-acetoxymethyl-2,2-dimethylcyclopropanecarboxaldehyde having theformula XVII ##STR16## Oxidation of the above compound yields3-acetoxymethyl-2,2-dimethylcyclopropanecarboxylic acid, useful for thepreparation of ester pest control agents of the invention wherein R¹ isacetyl and X is --C(O)OR in which R is a group of the formulas I-VI,inclusive.

The ozonolysis reactions are conducted with a gaseous mixture comprisingozone and oxygen or ozone and air. The mixture of ozone and oxygen issuitably diluted with an inert gas, such as nitrogen or argon. Theozonolysis is carried out at a temperature from about -80° C. to +20°C., preferably from about -20° C. to +20° C. It is useful in certaincases to use a solvent. Suitable solvents include aromatic hydrocarbonssuch as benzene and toluene, halogenated hydrocarbons, such as methylenedichloride, chloroform, and the like, lower aliphatic carboxylic acidsand esters thereof such as glacial acetic acid, ethyl acetate, and thelike, aliphatic hydrocarbons, such as n-hexane and the like, and loweralkanols such as methanol.

Oxidation of the compound of formulas VIII, XIV and XVII is conductedusing reagents which convert an aldehyde into an ester or acid group asrequired. For example, the compound of formula VIII is oxidized byhydrogen peroxide, or a peracid, such as m-chloroperbenzoic acid,perbenzoic acid, perphthalic acid, and the like, in a suitable solventsuch as chlorinated hydrocarbon, e.g., chloroform or dichloroethylene,or an ether, e.g., diethyl ether, and the compounds of formulas XIV andXVII are oxidized using potassium permanganate, chromic acid, potassiumdichromate or the like. Such oxidations are conveniently carried out inthe liquid phase by agitating, e.g., stirring a mixture of thereactants, preferably in a solvent such as an acetone-water mixture. Thereaction is conducted at a temperature of from about 0° C. to about 60°C. at normal pressures. Preferably, the reactions are conducted at atemperature of from about 10° C. to about 40° C.

The acetate derivative of formula IX is converted into thecyclopropylmethanol derivative of formula X by hydrolysis, preferablyunder basic conditions, for example using an alkali or alkaline earthmetal hydroxide or carbonate, such as sodium hydroxide, potassiumhydroxide, sodium carbonate or the like, in an aqueous alcoholicreaction medium, such as aqueous methanol, ethanol or the like.

The hydroxy group of derivative of formula X is converted into an ethergroup by treatment with an optionally substituted hydrocarbyl halide, R¹Hal in which R¹ is a group as previously defined and Hal is chlorine,bromine or iodine. Such treatment is suitably in the presence of analkali metal hydride, such as sodium hydride or potassium hydride,preferably in the presence of an inert solvent, such as tetrahydrofuran,dimethylformamide, and the like, or in the presence of a hydrocarbyllithium compound, such as an alkyl, aryl or aralkyl lithium compound,e.g., n-butyl lithium and the like, another preferably in the presenceof an inert solvent, such as tetrahydrofuran, and the like.

The acetals IX and XI are converted into the aldehydes of formulas XVand XII, respectively, by treatment with an acidic material in anaqueous environment. Preferred acidic materials are acetic acid orhydrochloric acid used in the form of an aqueous solution thereof.

The compounds of formulas XV and XII are converted into esterderivatives of formulas XVI and XIII, respectively, by treatment withthe appropriate carboxylic acid anhydride, e.g., acetic anhydride, inthe presence of a basic material. Suitable basic materials includetertiary amines, and alkali acetates. Preferred amines are pyridine andespecially triethylamine.

The acetate derivatives of formulas XVI and XIII are converted to thealdehydes of formulas XVII and XIV, respectively, by ozonolysis aspreviously described and by treatment with zinc in the presence ofacetic acid or with a basic material, preferably triethylamine, usuallyin an inert solvent, such as methylene chloride or the like.

The alcohols from which the groups of formulas I through VI, inclusive,are known in the art, as for example in Elliott et al. U.S. Pat. No.3,922,269 or Belgian Pat. No. 839,360. The pest control esters of thepresent invention can be prepared by esterification involving thereaction of an alcohol or derivative thereof of formula RQ, e.g., offormula IV, and a cyclopropanecarboxylic acid or derivative of formulaXVIII ##STR17## wherein Q and COP are functional groups or atoms whichwill react to form an ester linkage and R¹, D, Z, Z¹ and Z² are asdefined above.

It is usually convenient in practice either to treat the acid or acidhalide with the alcohol (COP═COOH or CO-halide and Q═OH) or to treat ahalogeno compound (Q═halogen) with a salt of the carboxylic acid(COP═COO--M) where M is, for example, a silver or ammonium cation.

It can be useful to prepare the intermediate alkyl ester as tert-butylester (R═tert-butyl), which can be selectively converted under acidconditions as mentioned earlier to give the free acid which can beesterified, e.g., after conversion to the acid halide, to a pesticidalester.

Suitable routes to the esters in which D is ##STR18## are similar tothose described in Belgian Pat. No. 839,360. One route involves treatingthe corresponding nitrile (D is --CN) with hydrogen sulfide in thepresence of a basic catalyst, preferably in the presence of a solvent.Useful solvents are lower alkanols, pyridine, or preferably a dipolaraprotic solvent, such as dimethylformamide or hexamethylphosphoramide.The catalyst is preferably a strong nitrogeneous base, particularly atertiary amine such as triethylamine, trimethylamine, or the like, or analkanolamine, such as triethanolamine, and the like. The reaction can becarried out at room temperature. It is desirable that the reactionsolution be saturated with hydrogen sulfide.

Alcohols of formula RQ where R is a group of formula IV may be preparedby reduction of the corresponding acids, esters or aldehydes e.g., withhydride, or by conversion of the corresponding halide to an ester, e.g.,by reaction with sodium acetate, followed by hydrolysis of the ester, orby reaction with formaldehyde of a Grignard reagent derived from thecorresponding halide. The halides of formula RQ where R is a group offormula IV can be prepared by halomethylation of the compound ##STR19##or side chain halogenation of ##STR20##

As stated earlier, the esters wherein R¹ is an acetyl or optionallysubstituted hydrocarbyl group are useful pest control agents having theability to knockdown insects, such as houseflies, or repel mites and/orto kill insects or mites. The particular mode of pest control activity(high knockdown, repelling or killing action) can vary with theindividual cyclopropanecarboxylate ester of the invention and thusdepends on the specific combination of acid and alcohol moieties. Ingeneral, the pest control mode of action of the esters of the inventionwherein R¹ is acetyl is knockdown or mite repelling rather than akilling action. In the esters wherein R¹ is optionally substitutedhydrocarbyl, high knockdown is present and often mite repelling,insecticidal and acaricidal activity as well.

The invention includes, within its scope, pest control compositionscomprising an agriculturally acceptable adjuvant--that is, at least onecarrier or a surface-active agent--and, as active ingredient, at leastone pest control ester of this invention. Likewise, the inventionincludes also a method of controlling insect, acarine or other arthropodpests at a locus which comprises applying to the pests or to the locus apest controlling effective amount of at least one ester of theinvention.

With respect to the spectrum of pesticidal activity, the compounds ofthis invention exhibit a selective or non-selective activity asinsecticides or acaricides against one or more species of such orders asColeoptera, Lepidoptera (especially larvae), Diptera, Orthoptera,Hemiptera, Homoptera and Acarina depending upon the specific combinationof acid and alcohol moieties according to the present invention. Thecompositions according to the present invention are useful forcontrolling one or more disease carrying insects such as mosquitos,flies and cockroaches, grain insects such as rice weevil (Sitophilusoryzae) and mites as well as agricultural noxious insects such asplanthoppers, green rice leafhopper (Nephotettix bipuntatus cinticepsUhler), diamond-back moths (Plutella maculipennis Curtis), importedcabbage worm (Pieris rapae Linne), rice stem borers (Chilo suppressalisWalker), corn earworm larvae (Heliothis zea Boddie), aphids, tortrixes,leaf-miners and the like.

The pesticidal esters of the invention are used for harvested crops,horticultural application, forests, cultures in green house, andpackaging materials for foodstuffs.

The term "carrier" as used herein means a material that may be inorganicor organic and of synthetic or natural origin with which the activecompound is mixed or formulated to facilitate its application to theplant, seed, soil and other object to be treated, or its storage,transport or handling. The carrier may be a solid or a liquid.

Suitable solid carriers may be natural and synthetic clays andsilicates, for example, natural silicas such as diatomaceous earths;magnesium silicates, for example, talcs; magnesium aluminum silicates,for example, attapulgites and vermiculites; aluminum silicates, forexample, kaolinites, montmorillonites and micas; calcium carbonate;calcium sulfate; synthetic hydrated silicon oxides and synthetic calciumor aluminum silicates; elements such as for example, carbon and sulfur;natural and synthetic resins such as, for example, coumarone resins,polyvinyl chloride and styrene polymers and copolymers; solidpolychlorophenols; bitumen, waxes such as beeswax, paraffin wax, andchlorinated mineral waxes; degradable organic solids, such as groundcorn cobs and walnut shells; and solid fertilizers, for examplesuperphosphates.

Suitable liquid carriers include solvents for the compounds of thisinvention and liquids in which the toxicant is insoluble or onlyslightly soluble.

Examples of such solvents and liquid carriers, generally, are water,alcohols, for example, isopropyl alcohol, ketones, such as acetone,methyl ethyl ketone, methyl isobutyl ketone and cyclohexanone; ethers;aromatic hydrocarbons such as benzene, toluene and xylene; petroleumfractions, such as kerosene, light mineral oils, chlorinatedhydrocarbons, such as methylene chloride, perchlorethylene,trichloroethane, including liquified normally vaporous gaseouscompounds. Mixtures of different liquids are often suitable.

If used, the surface-active agent may be an emulsifying agent or adispersing agent or a wetting agent. It may be nonionic, ionic orpreferably, mixtures of both. Surface-active agents usually applied informulating pesticides may be used. Examples of such surface-activeagents are the sodium or calcium salts of polyacrylic acids and ligninsulfonic acids; the condensation products of fatty acids or aliphaticamines or amides containing at least 12 carbon atoms in the moleculewith ethylene oxide and/or propylene oxide; fatty acid esters ofglycerol, sorbitan, sucrose or pentaerythritol; fatty acids salts of lowmolecular weight, mono-, di-, and trialkyl-amines; condensates of thesewith ethylene oxide and/or propylene oxide; condensation products offatty alcohols or alkyl phenols, for example, p-octylphenol orp-octylcresol, with ethylene oxide and/or propylene oxide; sulfates orsulfonates of these condensation products; alkali or alkaline earthmetal salts, preferably sodium salts of sulfonated castor oil, andsodium alkylaryl sulfonates such as sodium dodecylbenzene sulfonate; andpolymers of ethylene oxide and copolymers of ethylene oxide andpropylene oxide.

The compositions of the invention may be formulated as wettable powders,dusts, granules, solutions, emulsifiable concentrates, emulsions,suspension concentrates or aerosols. Encapsulated formulations andcontrolled release formulations are also contemplated, as are baitformulations. Wettable powders are usually compounded to contain 25, 50or 75% w of toxicant and usually contain, in addition to solid carrier,3-10% w of stabilizer(s) and/or other additives such as penetrants orstickers. Dusts are usually formulated as a dust concentrate having asimilar composition to that of a wettable powder but without adispersant, and are diluted in the field with further solid carrier togive a composition usually containing 1/2-10% w of toxicant. Granulesmay be manufactured by extrusion of plastics, agglomeration orimpregnation techniques. Generally, granules will contain 1/2-25% wtoxicant and 0-10% w of additives such as stabilizers, slow releasemodifiers and binding agents. Emulsifiable concentrates usually contain,in addition to the solvent, and when necessary, cosolvent, 10-50% w/vtoxicant, 2-20% w/v emulsifiers and 0-20% w/v of appropriate additivessuch as stabilizers, penetrants and corrosion inhibitors. Suspensionconcentrates are compounded so as to obtain a stable, nonsedimenting,flowable product and usually contain 10-75% w toxicant, 0-5% w ofdispersing agents, 0.1-10% w of suspending agents such as protectivecolloids and thixotropic agents, 0-10% w of appropriate additives suchas defoamers, corrosion inhibitors, stabilizers, penetrants andstickers, and as carrier, water or an organic liquid in which thetoxicant is substantially insoluble; certain organic additives orinorganic salts may be dissolved in the carrier to assist in preventingsedimentation or as antifreeze agents for water.

Aqueous dispersions and emulsions, for example, compositions obtained bydiluting a wettable powder or an emulsifiable concentrate according tothe invention with water, also lie within the scope of the presentinvention.

The compositions of the invention can also contain other ingredients,for example, other compounds possessing pesticidal, herbicidal orfungicidal properties, or attractants, such as pheromones, attractivefood ingredients, and the like, for use in baits and trap formulations.

Particularly useful compositions can be obtained by using a mixture oftwo or more kinds of the present compounds, or by the use of synergists,such as those known for use with the general class of "pyrethroid"compounds, especiallyα-[2-(2-butoxyethoxy)ethoxy]-4,5-methylenedioxy-2-propyltoluene alsoknown as piperonyl butoxide,1,2-methylenedioxy-4-[2-(octylsulfinyl)propyl]benzene,4-(3,4-methylenedioxyphenyl)-5-methyl-1,3-dioxane also known assafroxane, N-(2-ethyhexyl)bicyclo-[2,2,1]hept-5-ene-2,3-dicarboximide,octachlorodipropyl ether, isobornyl thiocyanoacetate, and othersynergists used for allethrin and pyrethrin. Useful compositions can beprepared with other biological chemicals including othercyclopropanecarboxylates, organic phosphate type insecticides andcarbamate type insecticides.

The compositions of the invention are applied in sufficient amount tosupply the effective dosage of active ingredient at the locus to beprotected. This dosage is dependent upon many factors, including thecarrier employed, the method and conditions of application, whether theformulation is present at the locus in the form of an aerosol, or as afilm, or as discrete particles, the thickness of film or size ofparticles, the insect or acarine species to be controlled and the like,proper consideration and resolution of these factors to provide thenecessary dosage of active material at the locus being within the skillof those versed in the art. In general, however, the effective dosage ofactive ingredient of this invention at the locus to be protected--i.e.,the applied dosage--is of the order or 0.01% to 0.5% based on the totalweight of the formulation, though under some circumstances the effectiveconcentration will be as little as 0.001% or as much as 2%, on the samebasis.

ILLUSTRATIVE EMBODIMENTS

The invention is illustrated by the following embodiments which describethe preparation of typical species of the invention. The embodiments arepresented for the purpose of illustration only and should not beregarded as limiting the invention in any way. The identity of theproducts, including intermediates, was confirmed by elemental, infraredand nuclear magnetic resonance spectral (NMR) analyses as necessary.

Embodiment 1(1R,cis)-1-(2,2-Dimethoxyethyl)-2,2-dimethyl-3-(2-oxopropyl)cyclopropane

Ozone was passed through 81.6 g of (+)-Δ³ -carene in 140 ml of methanolat -70° C. at a rate of 3 l/min for about 6 hours until appearance of ablue color indicated an excess of ozone was present in the reactionmixture. The reaction mixture was purged with air to remove excess ozoneand 60 ml of methyl sulfide was added. The resulting mixture was stirredand slowly warmed to room temperature overnight, at which time thereaction mixture gave a negative test to starch-iodide paper. Themethanol was stripped off and the product was diluted with 1 liter ofether, washed three times with 300 ml of water and then with 300 ml of asaturated sodium chloride solution. The resulting ether phase was driedwith magnesium sulfate, filtered and stripped to give 112.5 g of productas an oil, bp 98°-100° C. at 1 mm.

Embodiment 2((1R,cis)-(2-(2,2-Dimethoxyethyl)-3,3-dimethylcyclopropyl))methylacetate

To a stirred solution of the product from Embodiment 1 above in 1 literof methylene chloride at 20° C., was added 140 g of 70%m-chloroperbenzoic acid at 20°-30° C. over a period of 2 hours. Themixture was stirred at room temperature for an additional 18 hours,after which the excess peroxy acid was decomposed with 10% sodiumsulfite solution. The solid products were filtered and washed withmethylene chloride. The methylene chloride phase was washed twice with30 ml of saturated sodium bicarbonate solution and then with saturatedsodium chloride solution. The methylene chloride phase was then driedwith magnesium sulfate, filtered and stripped to give 125 g of an oilcontaining a small amount of solid material. This product was dilutedwith pentane and cooled in ice water. The resulting solid material wasfiltered and the remaining solution was stripped with an aspirator andpump to give 112.3 g of product as an oil, bp 98°-100° C. at 1 mm.

Embodiment 3((1S,cis)-2,2-Dimethyl-3-(2,2-dimethoxyethyl)cyclopropyl)methanol

A solution of 100 g of the product from Embodiment 2 above, 32 g of 85%potassium hydroxide, 15 ml of water and 600 ml of methanol was stirredat room temperature for about 18 hours. Methanol was then stripped andthe remaining reaction mixture was diluted with water. The resultingaqueous solution was extracted twice with chloroform. The combinedchloroform phases were washed with water and then with saturated sodiumchloride solution. The chloroform phase was dried with magnesiumsulfate, filtered and stripped to give 85 g of a yellow oil. This oilwas distilled to give 63 g of product, bp 73°-75° C. at 0.05 mm.

Embodiment 4(1R,cis)-3-(Ethoxymethyl)-2,2-dimethyl-1-(2,2-dimethoxyethyl)cyclopropane

To a stirred mixture of sodium hydride, from 5.8 g of 50% dispersion ofsodium hydride in mineral oil washed with pentane, and 200 ml of drydimethylformamide was added dropwise, at room temperature, 22.6 g of theproduct from Embodiment 3 above; mild gas evolution took place.Subsequently, 37.4 g of ethyl iodide was added dropwise at 10°-25° C.over a period of 1/2 hour during which time vigorous gas evolution wasobserved. After stirring for about 18 hours at room temperature, anadditional 6 g of sodium hydride in 100 ml of dimethylformamide wasadded and the reaction mixture was stirred at room temperature for 3days. The mixture was quenched with water after decomposing any excesssodium hydride with ethanol. The aqueous solution was extracted withether and the ether phase was washed with water. The ether phase wasthen dried with magnesium sulfate and stripped to give 30 g of an oil.This oil was distilled to give 20.3 g of desired product, bp 69°-70° C.at 0.2 mm.

Embodiments 5-7

Using procedures similar to those of Embodiment 4 above, the followingcyclopropane derivatives were prepared:3-methoxymethyl-2,2-dimethyl-1-(2,2-dimethoxyethyl)cyclopropane. bp 60°C. at 0.3 mm Hg; 3-propoxymethyl-(2,2-dimethoxyethyl)cyclopropane, bp75°-77° C. at 0.2 mm Hg; and3-benzyloxymethyl-1-(2,2-dimethoxyethyl)cyclopropane, bp 125°-130° C. at0.2 mm Hg.

Embodiment 8(1R,cis)-2,2-Dimethyl-3-(ethoxymethyl)cyclopropaneacetaldehyde

A 30 g solution of the acetal from Embodiment 4 above in 500 ml of a 2:1mixture of acetic acid and water was stirred at room temperature forabout 6 hours. The reaction mixture was poured into 1 liter of water.The aqueous mixture was extracted with methylene chloride, and themethylene chloride phase was washed with water, then with a saturatedsodium bicarbonate solution and finally with a saturated sodium chloridesolution. The methylene chloride phase was dried with magnesium sulfateand stripped to give 28 g of an oil. The oil was distilled to give 21.6g of product, bp 64°-66° C. at 0.5 mm and [α]_(D) ²⁵ +25.6° (CHCl₃);c=0.02 g/cc.

Embodiments 9-11

Using procedures similar to those of Embodiment 8 above, the followingcyclopropane derivatives were prepared:2,2-dimethyl-3-(methoxymethyl)cyclopropaneacetaldehyde, bp 55°-57° C. at0.3 mm Hg; 2,2-dimethyl-3-(propoxymethyl)cyclopropaneacetaldehyde, bp75°-78° C. at 1 mm Hg; and2,2-dimethyl-3-(benzyloxymethyl)cyclopropaneacetaldehyde, bp 115°-124°C. at 0.15-0.25 mm Hg.

Embodiment 12 ((1R,cis)-2,2-Dimethyl-3-(ethoxymethyl)cyclopropyl)vinylacetate

A solution of 20.5 g of the aldehyde from Embodiment 8 above, 60 ml ofacetic anhydride and 12.8 g of triethylamine was stirred at roomtemperature for 10 hours. The reaction mixture was diluted with ether,washed with ice water, ice cold 1N hydrochloric acid, ice cold solutionof sodium bicarbonate, and finally with saturated sodium chloridesolution. The ether phase was dried with magnesium sulfate, and strippedto give 52 g of an oil. After removal of acetic anhydride at 40° C. and10 mm Hg, the oil was distilled to give 15.2 g of product, bp 78°-80° C.at 0.3 mm Hg and [α]_(D) ²⁵ -36.2 (CHCl₃); c=0.02 g/cc.

Embodiments 13-15

Using procedures similar to those of Embodiment 12 above, the followingcyclopropane derivatives were prepared:2,2-dimethyl-3-(methoxymethyl)cyclopropyl vinyl acetate, bp 75°-77° C.at 0.5 mm Hg; 2,2-dimethyl-3-(propoxymethyl)cyclopropyl vinyl acetate,bp 85°-88° C. at 0.2 mm Hg; and2,2-dimethyl-3-(benzyloxymethyl)cyclopropyl vinyl acetate, bp 121°-127°C. at 0.03 mm Hg.

Embodiment 16(1R,cis)-2,2-Dimethyl-3-(ethoxymethyl)cyclopropanecarboxaldehyde

Ozone was passed through a stirred solution of 14.5 g of the acetatefrom Embodiment 12 above in 120 ml of methylene chloride at -70° C. at arate of 1 liter/min for 2 hours until the appearance of a blue colorindicated the presence of excess ozone. The reaction mixture was purgedwith air to remove excess ozone and the methylene chloride strippedbelow 20° C. The resulting product was diluted with 200 ml of ethercontaining 50 ml glacial acetic acid. The solution was treated at15°-25° C. with 25 g of zinc dust added portionwise over 1 hour. Thisreaction mixture was stirred for 1 hour at 25° C., filtered to removesalts and the solids were washed with ether. The combined etherfiltrates were washed with water, saturated sodium bicarbonate solutionand finally with saturated sodium chloride solution, dried withmagnesium sulfate, and stripped to give 11 g of an oil. This oil wasdistilled to give 8.4 g of product, bp 63°-66° C. at 1.5 mm Hg and[α]_(D) ²⁵ -46.7° (CHCl₃); c=0.02 g/cc.

Embodiments 17-19

Using procedures similar to those of Embodiment 16 above, the followingcyclopropane compounds were prepared:2,2-dimethyl-3-(methoxymethyl)cyclopropanecarboxaldehyde, bp 55°-58° C.at 1.5 mm Hg; 2,2-dimethyl-3-(propoxymethyl)cyclopropanecarboxaldehyde,bp 65°-67° C. at 0.5 mm Hg; and2,2-dimethyl-3-(benzyloxymethyl)cyclopropanecarboxaldehyde, bp 120°-123°C. at b 0.3 mm Hg.

Embodiment 20(1R,cis)-2,2-Dimethyl-3-(ethoxymethyl)cyclopropanecarboxylic acid

To a stirred solution containing 7.7 g of the aldehyde from Embodiment16 above in 100 ml of acetone and 20 ml of water was added portionwise,over 1/2 hour, 6 g of potassium permanganate while maintaining thetemperature at 5°-10° C. The resulting reaction mixture was allowed towarm to room temperature while stirring for 4 hours. The mixture wasfiltered, and the filtrate was decolorized with a 10% sodium bisulfite,and, after filtration adjusted to a pH of 4 by addition of concentratedhydrochloric acid. The solution was extracted with methylene chlorideand the extract was washed with water, and dried with magnesium sulfate.The solvent was stripped to give 6.4 g of a thick oily liquid.Crystallization from hexane gave 4.9 g of product as a colorless solid;mp 40°-40.5° C.

Embodiments 21-23

Using procedures similar to Embodiment 20 above, the following(1R,cis)-2,2-dimethyl-3-(hydrocarbyloxymethyl)cyclopropanecarboxylicacids were prepared:2,2-dimethyl-3-(methoxymethyl)cyclopropanecarboxylic acid, mp 42°-43°C.; 2,2-dimethyl-3-(propoxymethyl)cyclopropanecarboxylic acid, bp 100°C. at 0.05 mm Hg; and2,2-dimethyl-3-(benzyloxymethyl)cyclopropanecarboxylic acid, bp110°-120° C. at 0.05 mm Hg.

Embodiment 24 ((1S,cis)-(2,2-dimethyl-3-(2-oxoethyl)cyclopropyl))methylacetate

112 g of the product of Embodiment 2 above was treated with 1670 ml of a2:1 solution of acetic acid: water at room temperature for 15 hours. Thereaction mixture was poured into 2 liters of water and extracted twicewith 1 liter of methylene chloride. The methylene chloride phase waswashed with 2 liters of water and then with 500 ml of saturated sodiumbicarbonate solution. The resulting methylene chloride phase was driedwith magnesium sulfate and stripped to give 85 g of product as an oil,bp 75°-77° C. at 0.4 mm.

Embodiment 25((1R,cis)-2-(3-acetoxymethyl-2,2-dimethylcyclopropyl))vinyl acetate

85 g of the product from Embodiment 24 above was treated while stirringwith 99 g of triethylamine and 230 ml of acetic anhydride at roomtemperature for about 18 hours. The reaction mixture was diluted withether. The resulting solution was washed with ice water, then with icecold sodium bicarbonate solution and finally with saturated sodiumchloride solution. The ether phase was dried with magnesium sulfate andstripped to give 350 g of an oil. This oil was distilled to removeacetic anhydride at 40° C. and 10 mm Hg and the resulting residue wasdistilled to give 80 g of product: bp 93°-96° C. at 0.1 mm Hg.

Embodiment 26(1R,cis)-3-(acetoxymethyl)-2,2-dimethylcyclopropanecarboxaldehyde

Ozone was passed through 25 g of the product from Embodiment 25 above in150 ml methylene chloride at a rate of 3 l/min until appearance of ablue color indicated an excess of ozone was present in the reactionmixture. Ozone treatment was continued at a rae of 1 l/min for anadditional 40 minutes. The reaction mixture was purged with air toremove excess ozone and stripped below 25° to a clear pale yellow oil.This oil was dissolved in 250 ml acetic acid and 40 g of zinc dust wasadded portionwise over a 2 hour period at 10°-20° C. The resultingmixture was stirred 2 additional hours and then filtered through celite.The filtrate was washed with water, then with saturated sodiumbicarbonate solution and finally with a saturated sodium chloridesolution. The resulting solution was dried with magnesium sulfate andstripped to give 16.1 g of product as a colorless oil, bp 58°-60° C. at0.1 mm.

Embodiment 27(1R,cis)-2,2-Dimethyl-3-(acetoxymethyl)cyclopropanecarboxylic acid

To a solution of 21.0 g of the product of Embodiment 26 above, 250 ml ofacetone and 50 ml of water at 5° C., was added 14.8 g of potassiumpermaganate portionwise over 40 minutes at 5°-10° C. The reactionmixture was then warmed to room temperature while stirring for 6 hours.The mixture was filtered and the filtrate was treated with 10% sodiumbisulfite solution to destroy excess permanganate and, after filtration,stripped to remove acetone and adjusted to a pH of 4 with concentratedhydrochloric acid. The resulting solution was extracted three times with100 ml methylene chloride. The combined methylene chloride extracts werewashed with water, then with saturated sodium chloride solution, driedwith magnesium sulfate and stripped to give 19 g of a thick oil whichcrystallized upon cooling overnight. This product was triturated withcold pentane and filtered to give 13.7 g of product as a solid; mp78°-79° C.

Embodiment 28α-Cyano-3-phenoxybenzyl(1R,cis)-2,2-dimethyl-3-(acetoxymethyl)cyclopropanecarboxylate

A mixture of 1.1 g of the product from Embodiment 27 above, 0.6 g oftriethylamine, 1.7 g of α-cyano-3-phenoxybenzyl bromide in 10 ml ofethyl acetate was refluxed for 1.5 hours to form a white precipitate.The reaction mixture was cooled, washed with water and dried withmagnesium sulfate. The resulting mixture was chromatographed on silicagel using 5:1 pentane-ether as eluent to give 1.3 g of product as aviscous pale yellow oil; [α]_(D) ²⁵ 4.2° (CHCl₃); c=0.024 g/cc.

Embodiment 29α-Cyano-3-phenoxybenzyl(1R,cis)-2,2-dimethyl-3-(ethoxymethyl)cyclopropanecarboxylate

A mixture of 1.7 g of 2,2-dimethyl-3-ethoxymethylcyclopropanecarboxylicacid (as prepared in Embodiment 20), 2.9 g of α-cyano-3-phenoxybenzylbromide and 1 g of triethylamine in 25 ml of ethyl acetate was refluxedfor 3 hours. The reaction mixture was left standing at room temperatureovernight. The mixture was diluted with ether, washed with water andthen with saturated sodium chloride solution. The ether phase was driedwith magnesium sulfate and stripped to give 3.6 g of a thick oil. Thisoil was chromatographed on silica gel using a 5:1 pentane-ether solutionas eluent to give 2.8 g of the desired product as a thick yellow oil;[α]_(D) ²⁵ +23.8° (CHCl₃); c=0.02 g/cc.

Embodiment 30-33

Using procedures similar to those described in Embodiment 29 above, thefollowing cyclopropanecarboxylates were prepared:α-cyano-3-phenoxybenzyl(1R,cis)-2,2-dimethyl-3-(methoxymethyl)cyclopropanecarboxylate,3-phenoxybenzyl(1R,cis)-2,2-dimethyl-3-(ethoxymethyl)cyclopropanecarboxylate,α-cyano-3-phenoxybenzyl(1R,cis)-2,2-dimethyl-3-(propoxymethyl)cyclopropanecarboxylateandα-cyano-3-phenoxybenzyl(1R,cis)-2,2-dimethyl-3-(benzyloxymethyl)cyclopropanecarboxylate.

I claim:
 1. A (1R,cis) compound of the formula ##STR21## wherein R¹represents an acetyl group; an alkyl group containing from 1 to 10carbon atoms optionally substituted by one or more halogen atoms; a(cycloalkyl)alkyl group containing from 3 to 7 ring carbon atoms, atotal of from 4 to 9 carbon atoms and optionally ring-substituted by oneor more halogen atoms; a cycloalkyl group containing from 3 to 7 ringcarbon atoms; an alkenyl group containing from 2 to 4 carbon atomsoptionally substituted by one or more halogen atoms or alkynyl groupcontaining from 2 to 4 carbon atoms or an aryl group containing from 6to 12 carbon atoms or an aralkyl group containing from 7 to 10 carbonatoms, each optionally ring-substituted by one more halogen atoms; X is--CH₂ CH(OCH₃)₂, --CH₂ CHO, --CH═CHOR² in which R² is an acyl groupcontaining from 1 to 5 carbon atoms, --CHO, --C(O)Cl or --C(O)Br withthe proviso that when R' is acetyl then X is not --CH₂ CHO.
 2. Acompound according to claim 1 wherein R' is an alkyl group containingfrom 1 to 6 carbon atoms, a (cycloalkyl)alkyl group containing from 3 to6 ring carbon atoms and a total of 4 to 8 carbon atoms, a cycloalkylgroup containing from 3 to 6 carbon atoms, an alkenyl or alkynyl groupcontaining from 2 to 4 carbon atoms, an aryl group containing from 6 to12 carbon atoms or an aralkyl group containing from 7 to 10 carbonatoms.
 3. A compound according to claim 2 wherein R¹ is an alkyl groupcontaining from 1 to 3 carbon atoms or a benzyl group.
 4. A compoundaccording to claim 3 wherein X is --CH₂ CH(OCH₃)₂.
 5. A compoundaccording to claim 1 wherein R¹ is acetyl and X is --CH═CHOR² in whichR² is acetyl.
 6. A compound according to claim 1 wherein R¹ is acetyland X is --CHO. 7.(1R,cis)-(2,2-dimethoxyethyl-3,3-dimethylcyclopropyl)methyl acetate. 8.((1S,cis)-(2,2-dimethyl-3-(2-oxoethyl)cyclopropyl))methyl acetate. 9.(1R,cis)-3-(acetoxymethyl)-2,2-dimethylcyclopropanecarbaldehyde.